The presence of a specific allele for the serotonin transporter gene more than doubles the risk for depression following a significant life stress, according to an article in the July 18th issue of Science.

Dr. Avshalom Caspi and his American and British colleagues found the association between serotonin-related genes and depression that had been missed in 8 previous studies. "We found the connection only because we looked at the study members' stress history," noted Dr. Terrie Moffitt, a coauthor of the study. She suggested that measuring such pivotal environmental events -- which can include infections and toxins as well as psychosocial trauma -- might be the key to understanding the genetics underlying psychiatric disorders.

The short allele of the serotonin transporter gene produces less protein than the protective, long allele. Thus, people with the short allele have an increased level of serotonin in synapses and prolonged binding of neurotransmitter at the dendrites of adjacent cells. The authors hypothesize that these people may be at risk for depression because their brain chemistry is less efficient than normal at discontinuing neurotransmitter signals.

The researchers followed 847 Caucasian New Zealanders born in the early l970s from birth into adulthood. Genotypes in the cohort were similar to those in the general Caucasian population, with 17 percent homozygous for the short allele, 31 percent homozygous for the long allele, and 51 percent heterozygous for the gene.
Based on the hypothesis that the candidate allele would act through a gene-environment interaction, researchers charted study participants' stressful life events from ages 21 to 26 years, including debt problems, homelessness, a disabling injury, and being an abuse victim. Of the total of 847 adults, 30 percent had none, 25 percent had 1 event, 20 percent had 2 events, 11 percent had 3 events, and 15 percent had 4 or more such stressful life experiences.

At age 26 years, 17 percent of the participants had a diagnosis of major depression in the past year and 3 percent had either attempted or thought about suicide. Although people with a short allele who experienced 4 or more life stresses represented only 10 percent of the total, they accounted for nearly one quarter of the 133 cases of depression. Among participants with 4 or more life stresses, 33 percent with either 1 or 2 copies of the short allele and 43 percent homozygous for the allele developed depression, compared with 17 percent of people who were homozygous for the long allele.

A stressful life event predicted new-onset depression in people with at least 1 copy of the short allele, whereas such an event did not predict the onset of depression in people who were homozygous for the long allele.